Heavy metal- and odour-free nanoparticulate compositions

Patent metadata

Field	Value
Publication number	US-11970563-B2
Application number	US-201916969808-A
Country	US
Kind code	B2
Filing date	Feb 27, 2019
Priority date	Feb 27, 2018
Publication date	Apr 30, 2024
Grant date	Apr 30, 2024

Abstract

The present invention relates to a nanoparticulate composition comprising nanoparticles formed from an amphipathic block copolymer comprising a hydrophilic block and a hydrophobic block, where the nanoparticles are provided in the form of micelles, cylindrical worm structures or vesicles and the size of the nanoparticles is from 25 to 500 nm, wherein: the composition is substantially free of heavy metals and compounds comprising sulfur. Also disclosed herein is a method of forming said nanoparticulate composition by polymerization induced self-assembly (PISA) via non-transition-metal catalysed controlled radical polymerization (NTMC-CRP).

First claim

The invention claimed is:

1. A nanoparticulate composition comprising:
nanoparticles formed from an amphipathic block copolymer comprising a hydrophilic block and a hydrophobic block, where the nanoparticles are provided in the form of micelles, cylindrical worm structures or vesicles and the size of the nanoparticles is from 25 to 500 nm, wherein:
the composition is substantially free of compounds comprising sulfur;
the composition is substantially free of a heavy metal; and
the composition includes an active agent encapsulated in the nanoparticles.

2. The composition according to claim 1 , wherein the amphipathic block copolymers are terminated by a halogen atom.

3. The composition according to claim 1 , wherein the active agent is selected from one or more of the group consisting of vitamin C, peptides, glycerol, dyes, flavours, perfume oils, citronellal, silicon oils, organosilicons, pesticides, Beta-carotene and a pharmacologically active agent.

4. The composition according to claim 1 , wherein when the nanoparticles are in the form of a vesicle, the amphipathic block copolymer is arranged in the form of a membrane with an outer and inner surface, which inner surface defines a core region.

5. The composition according to claim 4 , wherein the core region comprises one or both of an active agent and a liquid.

6. The composition according to claim 4 , wherein the amphipathic block copolymer is arranged so that the outer and inner surface of the membrane are formed from the hydrophilic blocks of the copolymer.

7. The composition according to claim 6 , wherein one or more of the following apply:
(AA) the composition further comprises a hydrophilic active agent that is substantially encapsulated in the core region of the vesicle;
(BB) the composition further comprises a hydrophobic active agent that is substantially encapsulated in the membrane of the vesicle; or
(CC) the composition further comprises a polar liquid that is encapsulated in the core region of the vesicle.

8. The composition according to claim 4 , wherein the amphipathic block copolymer is arranged so that the outer and inner surface of the membrane are formed from the hydrophobic blocks of the copolymer.

9. The composition according to claim 8 , wherein one or more of the following apply:
(DD) the composition further comprises a hydrophobic active agent that is substantially encapsulated in the core region of the vesicle;
(EE) the composition further comprises a hydrophilic active agent that is substantially encapsulated in the membrane of the vesicle; or
(FF) the composition further comprises a non-polar liquid that is encapsulated in the core region of the vesicle.

10. The composition according to claim 1 , wherein one of the following applies:
(A) when the nanoparticles are in the form of a micelle, the amphipathic block copolymer has an average ratio of hydrophobic repeating units to hydrophilic repeating units of from 1:100 to 10:1 or vice versa; or
(B) when the nanoparticles are in the form of cylindrical worm structures, the amphipathic block copolymer has an average ratio of hydrophobic repeating units to hydrophilic repeating units of from 1:1 to 100:1 or vice versa.

11. The composition according to claim 1 , wherein the amphipathic block copolymer is a poly(acrylic acid-co-acrylate ester) or a poly((polyethylene glycol ether methacrylate)-co-acrylate ester.

12. The composition according to claim 1 , wherein the amphipathic block copolymer is crosslinked.

13. A method of forming a nanoparticulate composition according to claim 1 using polymerisation induced self-assembly, the method comprising the step of forming a block copolymer by reacting a monomeric material with a macroinitiator compound in the presence of an initiator compound, a catalyst and a solvent, wherein:
if the monomeric material polymerises to provide a hydrophobic polymer block, then the macroinitiator compound is a hydrophilic polymer or oligomer or if the monomeric material polymerises to provide a hydrophilic polymer block, then the macroinitiator compound is a hydrophobic polymer or oligomer;
the macroinitiator compound is terminated with a halogen atom;
the monomeric material, the macroinitiator compound, the initiator compound, the catalyst and the solvent are all substantially free of compounds comprising sulfur; and
the monomeric material, the macroinitiator compound, the initiator compound, the catalyst and the solvent are all substantially free of a heavy metal.

14. The method according to claim 13 , wherein:
(i) the monomeric material is an acrylate ester, and the macroinitiator compound is a poly(acrylic acid) or an oligo(acrylic acid); or
(ii) the monomeric material is an acrylic acid and the macroinitiator compound is a poly(acrylate ester) or an oligo(acrylate ester).

15. The method according to claim 13 , wherein the step of forming a block copolymer is conducted in the presence of a crosslinking agent.

16. The method according to claim 13 , wherein the step of forming a block copolymer is conducted in the presence of an active agent.

17. The method according to claim 13 , wherein after the nanoparticle has been formed an active agent is encapsulated into the nanoparticle by osmosis.

18. The method according to claim 13 , wherein one of the following applies:
(a) the nanoparticles are obtained as vesicles when the molar ratio of monomeric material to macroinitiator compound in the solvent is from 100:1 to 500:1, and the reaction is allowed to occur for a period of time such that an average ratio of monomeric material repeating units to macroinitiator repeating units from 1:9 to at least 9:1 is obtained;
(b) the nanoparticles are obtained as micelles when the molar ratio of monomeric material to macroinitiator compound in the solvent is from 40:1 to 100:1 and the reaction is allowed to occur for a period of time such that an average ratio of monomeric material repeating units to macroinitiator repeating units from 1:100 to 10:1 is obtained; or
(c) the nanoparticles are obtained as cylindrical worm structures when the molar ratio of monomeric material to macroinitiator compound in the solvent is from 40:1 to 200:1 and the reaction is allowed to occur for a period of time such that an average ratio of monomeric material repeating units to macroinitiator repeating units from 1:1 to 100:1 is obtained.

19. The method according to claim 13 , wherein the macroinitiator compound is formed by polymerising a monomeric material with a dormant initiator compound in the presence of an initiator compound, a catalyst and a solvent, wherein
the dormant initiator compound is a hydrocarbon comprising a halogen atom;
the monomeric material, the dormant initiator compound, the initiator compound, the catalyst and the solvent are all substantially free of compounds comprising sulfur; and
the monomeric material, the dormant initiator compound, the initiator compound, the catalyst and the solvent are all substantially free of a heavy metal.

Assignees

• Univ Nanyang Tech
• Agency Science Tech & Res

Inventors

• Goto Atsushi
• Sarkar Jit
• Xiao Longqiang
• Li Feifei
• Van Herk Alexander M
• Jackson Alexander William

Classifications

• C08F299/024 Primary

  the unsaturation being in acrylic or methacrylic groups · CPC title

• C08F4/08

  of alkali metals · CPC title

• C08F293/005 Primary

  using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent · CPC title

• A61K9/5138

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• B82Y30/00

  Nanotechnology for materials or surface science, e.g. nanocomposites · CPC title